Parkinson's disease (PD) is the most common serious movement disorder and affects over 1% of adults older than 60 years of age. In the United States alone, the total annual costs related to PD are estimated to exceed 6 billion dollars. With the increasing proportion of elderly in the population, PD represents a growing burden on our health care system. The early symptoms of PD are associated with a selective loss of dopamine neurons in the substantial nigra but the etiology of PD is unknown. Although early treatment of motor manifestations is usually quite successful, the disease continues to progress and the development of non-motor manifestations adds to disability. One strategy that is gaining increasing attention is the development of neuroprotective therapies that would slow, or halt progression. The application of neuroprotection would have maximal benefit applied early in the disease. This requires increasingly sensitive methods of detection and characterization of PD pathology. Imaging offers new opportunities for in vivo assessment of patients with PD, or at risk. In the past two decades, a number of MR imaging studies have been performed to detect changes in the morphology of deep brain nuclei associated with PD. Unfortunately, the results of these MR studies have been controversial and inconsistent, primarily because of MRI resolution limitations. Recent technical advances in 7T MR imaging now allows us to image deep brain nuclei with significantly improved contrast and resolution;thus, we are able to characterize and quantify pathological changes in these structures in PD. The primary objective of this proposal is to develop and evaluate methods for: (1) quantification and characterization of pathological changes in deep brain nuclei using 7T MRI and (2) determine the reliability of the quantification of changes over time through serial MRI scans. The rationale for this proposal is based on the fact that high resolution 7T MR imaging makes both reliable segmentation and quantification of deep brain nuclei possible as well as potentially permitting characterization of structural changes over time. This information ultimately will help advance our understanding of the progression of PD and contribute to the development new methods to monitor the effects of new therapies. This proposed research is innovative in that we have applied new 7T MR imaging and segmentation techniques which can quantify changes in deep brain nuclei morphology in association with PD. Our central hypothesis is that MR will permit a precise in vivo structural analysis of PD pathology that will correlate closely with clinical manifestations. The specific aims of this proposal are to evaluate and compare: (1) the measurement reliabilities (between and within observers) of deep brain structures in PD patients imaged with 7T MR;and (2) the differences in the deep brain structures between PD and control subjects through a cross- sectional study. A secondary exploratory aim is to measure specific structural changes (and disease progression) over time to determine the sample size required for a future longitudinal study. PUBLIC HEALTH RELEVANCE: With the significantly improved image contrast and resolution offered by 7T MR images, we will develop and optimize MR imaging techniques to allow for reliable measurement of deep brain structures in patients with Parkinson disease. This will help advance our understanding of the structure-function relationships in the disease progression of Parkinson disease.